全文获取类型
收费全文 | 3910篇 |
免费 | 401篇 |
国内免费 | 1篇 |
出版年
2023年 | 11篇 |
2022年 | 57篇 |
2021年 | 84篇 |
2020年 | 54篇 |
2019年 | 47篇 |
2018年 | 86篇 |
2017年 | 81篇 |
2016年 | 132篇 |
2015年 | 234篇 |
2014年 | 229篇 |
2013年 | 267篇 |
2012年 | 325篇 |
2011年 | 351篇 |
2010年 | 229篇 |
2009年 | 182篇 |
2008年 | 261篇 |
2007年 | 266篇 |
2006年 | 241篇 |
2005年 | 174篇 |
2004年 | 162篇 |
2003年 | 168篇 |
2002年 | 148篇 |
2001年 | 33篇 |
2000年 | 22篇 |
1999年 | 40篇 |
1998年 | 34篇 |
1997年 | 18篇 |
1996年 | 12篇 |
1995年 | 16篇 |
1994年 | 10篇 |
1993年 | 10篇 |
1992年 | 18篇 |
1991年 | 11篇 |
1990年 | 21篇 |
1989年 | 13篇 |
1988年 | 20篇 |
1987年 | 23篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1983年 | 12篇 |
1982年 | 14篇 |
1981年 | 16篇 |
1980年 | 11篇 |
1977年 | 10篇 |
1976年 | 14篇 |
1975年 | 18篇 |
1974年 | 22篇 |
1973年 | 8篇 |
1972年 | 15篇 |
1970年 | 10篇 |
排序方式: 共有4312条查询结果,搜索用时 15 毫秒
951.
952.
953.
Rahel Decker Christoph Burdelski Melanie Zobiak Henning Büttner Gefion Franke Martin Christner Katharina Sa? Bernd Zobiak Hanae A. Henke Alexander R. Horswill Markus Bischoff Stephanie Bur Torsten Hartmann Carolyn R. Schaeffer Paul D. Fey Holger Rohde 《PLoS pathogens》2015,11(3)
Virulence of the nosocomial pathogen Staphylococcus epidermidis is crucially linked to formation of adherent biofilms on artificial surfaces. Biofilm assembly is significantly fostered by production of a bacteria derived extracellular matrix. However, the matrix composition, spatial organization, and relevance of specific molecular interactions for integration of bacterial cells into the multilayered biofilm community are not fully understood. Here we report on the function of novel 18 kDa Small basic protein (Sbp) that was isolated from S. epidermidis biofilm matrix preparations by an affinity chromatographic approach. Sbp accumulates within the biofilm matrix, being preferentially deposited at the biofilm–substratum interface. Analysis of Sbp-negative S. epidermidis mutants demonstrated the importance of Sbp for sustained colonization of abiotic surfaces, but also epithelial cells. In addition, Sbp promotes assembly of S. epidermidis cell aggregates and establishment of multilayered biofilms by influencing polysaccharide intercellular-adhesin (PIA) and accumulation associated protein (Aap) mediated intercellular aggregation. While inactivation of Sbp indirectly resulted in reduced PIA-synthesis and biofilm formation, Sbp serves as an essential ligand during Aap domain-B mediated biofilm accumulation. Our data support the conclusion that Sbp serves as an S. epidermidis biofilm scaffold protein that significantly contributes to key steps of surface colonization. Sbp-negative S. epidermidis mutants showed no attenuated virulence in a mouse catheter infection model. Nevertheless, the high prevalence of sbp in commensal and invasive S. epidermidis populations suggests that Sbp plays a significant role as a co-factor during both multi-factorial commensal colonization and infection of artificial surfaces. 相似文献
954.
955.
Induction of Complementary Function Reductase Enzymes in Colon Cancer Cells by Dithiole‐3‐thione versus Sodium Selenite
下载免费PDF全文
![点击此处可从《Journal of biochemical and molecular toxicology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Melanie M. Erzinger Cédric Bovet Anuli Uzozie Shana J. Sturla 《Journal of biochemical and molecular toxicology》2015,29(1):10-20
Cellular induction of reductase enzymes can alter the susceptibility of cells toward drugs and chemicals. In this study, we compared the capacity of a single dose of sodium selenite and 3H‐1,2‐dithiole‐3‐thione (D3T) to influence the drug‐relevant reducing capacity of HT29 cells over time, and defined the protein‐specific contribution to this activity on the basis of selected reaction monitoring mass spectrometry. Thioredoxin reductase 1 (TrxR1) protein levels and activity were inducible up to 2.2‐fold by selenium. In contrast, selenium had only a minor influence on prostaglandin reductase 1 (PTGR1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) activity and protein levels. D3T, a strong Nrf2 inducer, induced all the reductases and additionally increased the cytotoxicity of hydroxymethylacylfulvene, a bioreductive DNA‐alkylating drug. The data and experimental approaches allow one to define induction potency for reductase enzymes PTGR1, TrxR1, and NQO1 in HT29 cells and link these to changes in drug cytotoxicity. 相似文献
956.
957.
958.
High cell density cultivation of human leukemia T cells (Jurkat cells) in semipermeable polyelectrolyte microcapsules
下载免费PDF全文
![点击此处可从《Engineering in Life Science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Melanie Werner Daria Schmoldt Frank Hilbrig Valérie Jérôme Kenny Zambrano Holger Hübner Rainer Buchholz Ruth Freitag 《Engineering in Life Science》2015,15(4):357-367
The ex vivo expansion of human T cells is of considerable scientific and medical interest. Currently, this requires the addition of massive amounts of stimuli. Here, human leukemia T cells (Jurkat cells) were used as model cells to demonstrate the in vitro expansion of T cells in the absence of added stimuli after encapsulation in semipermeable sodium cellulose sulfate/poly(diallyldimethyl) ammonium chloride polyelectrolyte membrane capsules (molecular weight cutoff <10 kDa, average diameter ca. 800 μm). For comparison, free and encapsulated cells were cultivated in standard T‐flasks and spinner bottles (both 50 mL culture medium) as well as in hanging drops (35 μL, only nonencapsulated cells). Encapsulation led to a significantly higher specific growth rate, a prolonged exponential growth phase together with a reduced tendency for apoptosis, as evidenced by shifts in the cell cycle distribution toward the S and G2/M phases together with a reduced percentage of cells in the sub‐G0/G1 phase. As a consequence, very high cell densities (>140×106 cells/mLcapsule) were obtained in the capsules, particularly for the spinner cultivations. No evidence for nonspecific activation/stimulation, that is IL‐2 and CD25 expression, was found, while specific stimulation by phorbol‐12‐myristate‐13‐acetate/ionomycin was still possible. Since Jurkat cells commonly serve as model cells for primary T lymphocytes, the proposed method may present a strategy for high‐density proliferation of primary human T lymphocytes. 相似文献
959.
960.
EL Gautier A Chow R Spanbroek G Marcelin M Greter C Jakubzick M Bogunovic M Leboeuf N van Rooijen AJ Habenicht M Merad GJ Randolph 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(5):2614-2624
Although peroxisome proliferator-activated receptor γ (PPARγ) has anti-inflammatory actions in macrophages, which macrophage populations express PPARγ in vivo and how it regulates tissue homeostasis in the steady state and during inflammation remains unclear. We now show that lung and spleen macrophages selectively expressed PPARγ among resting tissue macrophages. In addition, Ly-6C(hi) monocytes recruited to an inflammatory site induced PPARγ as they differentiated to macrophages. When PPARγ was absent in Ly-6C(hi)-derived inflammatory macrophages, initiation of the inflammatory response was unaffected, but full resolution of inflammation failed, leading to chronic leukocyte recruitment. Conversely, PPARγ activation favored resolution of inflammation in a macrophage PPARγ-dependent manner. In the steady state, PPARγ deficiency in red pulp macrophages did not induce overt inflammation in the spleen. By contrast, PPARγ deletion in lung macrophages induced mild pulmonary inflammation at the steady state and surprisingly precipitated mortality upon infection with Streptococcus pneumoniae. This accelerated mortality was associated with impaired bacterial clearance and inability to sustain macrophages locally. Overall, we uncovered critical roles for macrophage PPARγ in promoting resolution of inflammation and maintaining functionality in lung macrophages where it plays a pivotal role in supporting pulmonary host defense. In addition, this work identifies specific macrophage populations as potential targets for the anti-inflammatory actions of PPARγ agonists. 相似文献